Orthomolecular Medicine for Everyone. Abram Hoffer, M.D., Ph.D.
sometimes black, discoloration of the parts of the body exposed to the sun. It has the appearance of a chronic suntan or sunburn. This is probably a primary tryptophan deficiency. Diarrhea may alternate with constipation. Of course, it increases malabsorption and aggravates the condition. Dementia is an organic dementia with confusion, disorientation, and memory disturbance. This is the typical terminal psychosis.
Earlier stages are more typically schizophrenic, with perceptual changes, disordered thoughts, and mood changes; psychotic behavior is common. At one time, over 25 percent of spring admissions to mental hospitals in the southern United States were psychotic pellagrins. There was no way of distinguishing them from other schizophrenic syndromes until vitamin B3 came into clinical use. If these patients responded quickly to the vitamin, they were diagnosed with pellagra; if not, they were diagnosed with schizophrenia. This practical diagnostic test had a very important deleterious consequence—it effectively quenched any interest in using vitamin B3 as a treatment for schizophrenia until double-blind, controlled studies in the 1950s.3 It would have been more appropriate to recognize the pellagra psychosis as one of the schizophrenia syndromes and to classify these patients as fast or slow responders to small doses or megadoses of vitamin B3.
The intermediate stage of pellagra is characterized by a variety of syndromes representing any of a large number of psychiatric, nonpsychotic states. Early pellagrologists considered neuroses one of the variants of subclinical pellagra, this in-between state. Another form is the syndrome affecting children that produces the hyperactive or learning-disordered child. The severe forms of pellagra take more of a neurological form (organic psychoses or toxic confusional states) and these may be a main factor in some senile psychoses. Huntington’s disease has been described as one of the expressions of pellagra.4
Pellagra has several causes. First, it is caused by a deficiency of tryptophan. Normally, this amino acid is the major precursor of vitamin B3; about 1–2 milligrams (mg) of B3 is made from 60 mg of tryptophan. There is evidence that tryptophan deficiency may be the cause of the typical skin dermatitis of pellagra: the dermatitis of pellagrins given tryptophan healed more rapidly than when they were give vitamin B3 only. Second, pellagra is caused by a deficiency of vitamin B3, caused by diets that contain too much corn or that depend too heavily on other food which has been processed (such as flour) or which is naturally low in this vitamin. A third cause of pellagra is a deficiency of pyridoxine (vitamin B6). Pyridoxine must be present before tryptophan can be converted to NAD. Diets deficient in B6 are as pellagragenic as diets deficient in vitamin B3.
Fourth, pellagra is caused by excessive loss of vitamin B3 in urine. NAD is made from tryptophan, niacinamide, and niacin. If too much vitamin B3 is lost, insufficient NAD will be made. The loss of vitamin B3 is under the control of the ratio of the amino acids isoleucine and leucine. Isoleucine decreases loss of B3, while leucine increases it. Ideally, foods should contain more isoleucine, but in most there is slightly more leucine. Excessive leucine causes pellagra and isoleucine is an anti-pellagra factor. Corn is the ideal pellagra-producing food, for it is low in tryptophan, low in vitamin B3, and too high in leucine compared to isoleucine.
Arthritis
The world was still deep in the Great Depression when William Kaufman, Ph.D., M.D., began treating osteoarthritis with 2–4 g (2,000–4000 mg) of niacinamide daily. Now, nearly seventy years later, his pioneering work in orthomolecular medicine is receiving the recognition it so well deserves. By 1950, Dr. Kaufman had already published two books detailing the beneficial effects of vitamin B3 for arthritis. Dr. Kaufman presented meticulous case notes for hundreds of patients, along with specific niacinamide dosage information applicable to both osteoarthritis and rheumatoid arthritis. In addition, he added some remarkably prescient observations on the antidepressant/antipsychotic properties of B3.
Dr. Kaufman, known as a conservative physician, was nevertheless the first to prescribe as much as 5,000 mg of niacinamide daily, in many divided doses, to improve range of joint motion. In previously unpublished comments, Dr. Kaufman noted that “niacinamide is a systemic therapeutic agent. It measurably improves joint mobility, muscle strength, (and) decreases fatigability. It increases maximal muscle working capacity, (and) reduces or completely eliminates arthritic joint pain.”
Regarding dosage, he stated that “the (more frequent) 250 mg dose of niacinamide is 40 to 50 percent more effective in the treatment of arthritis than the (less frequent) 500 mg dose. Niacinamide (alone or combined with other vitamins) in a thousand patient-years of use has caused no adverse side effects.” But he also urged a conservative approach: “Some joints are so injured by the arthritic process that no amount of niacinamide therapy will cause improvement in joint mobility, but it takes three months of niacinamide therapy before you can conclude this, since some joints are slow to heal.”5
In his book The Common Form of Joint Dysfunction, Dr. Kaufman stated that “It has been demonstrated empirically that even persons eating a good or excellent diet according to present-day standards exhibit measurable impairment in ranges of joint movement which tends to be more severe with increasing age. It has also been demonstrated that when such persons supplement their good or excellent diets with adequate amounts of niacinamide, there is, in time, measurable improvement in ranges of joint movement, regardless of the patients’ ages. In general, the extent of recovery from joint dysfunction of any given degree of severity depends largely on the duration of adequate niacinamide therapy.”6
One of Dr. Kaufman’s patients was so severely arthritic that he could not bend his elbows enough for a blood pressure measurement. Dr. Kaufman gave him niacinamide for a week in divided doses, and then he could bend his arm. After then taking him off the B3 and giving him a look-alike medicine (placebo) for a week, the patient was back where he started: his joints were stiff again. “I arrived at my (megavitamin B3 dosage) schedule by actually seeing the response of patients with varying degrees of arthritis,” stated Dr. Kaufman. “One cannot give a single large dose and get any really favorable results in arthritis … It is necessary to divide the doses so that the blood levels of niacinamide would be fairly uniform throughout the waking day.”7
His findings were both plain and elegant: the greater the stiffness, the more frequent the doses. Severely crippled arthritic patients needed up to a total of 4,000 mg per day, divided into ten doses. In one to three months, patients could now get out of their chair or bed. “If continued, they would be able comb their hair and be able to walk upstairs, so they would no longer be prisoners of the house. By the end of about three years’ treatment, they would be fully ambulatory, and this was even in the older age groups.”8
Schizophrenia
In 1952, Dr. Humphry Osmond and I (A. H.) started a double-blind experiment comparing niacin, niacinamide, and placebo on a group of thirty acute schizophrenic patients. The sickest patients from each group (more depressed or more violent) also received a short series of electroconvulsive therapy. One year after discharge, each patient was reevaluated. From the placebo group, three patients were well (the usual spontaneous recovery rate is considered to be about 35 percent). The other two groups fared better: from each, about 75 percent were well, doubling the one-year natural recovery rate. Three more double-blind experiments confirmed these conclusions. Since then, the use of vitamin B3 has become standard practice for orthomolecular therapists, but it is important to note that vitamin B3 alone is seldom used for treating schizophrenia. It is usually combined with orthomolecular nutrition, with other vitamins and minerals, and for a while with standard neuroleptic drugs when they are required. This comprehensive program has been used on over 100,000 schizophrenics in North America